IP Library › Granted Patent US 12,201,593
Granted Patent B2
US 12,201,593 · App. 17/256,212 · Granted Jan 21, 2025

Oral pharmaceutical formulations of bitter compounds for asthma

Inventors: Tien-Li Lee (San Diego, CA); Zhenhuan Zheng (San Diego, CA)
Assignee: Aardvark Therapeutics Inc.
A61K31/167A61K9/0053A61K31/136A61P11/06
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Quick Facts
Patent No.
US 12,201,593
App. No.
17/256,212
Granted
Jan 21, 2025
Kind
B2
Abstract

There is disclosed an oral pharmaceutical formulation of bitter compounds that are agonists of TAS2R receptors for the treatment of asthma. More specifically, the present disclosure provides an asthma oral formulation comprising a bitter agent selected from the group consisting of denatonium benzoate (DB), denatonium chloride (DC), denatonium saccharide (DS), denatonium acetate (DA), and combinations thereof and formoterol.

Claims (12)

1. A synergistic formulation comprising a bitter agent and formoterol, wherein the bitter agent is chosen from denatonium acetate (DA), denatonium citrate (DC), denatonium maleate (DM), and combinations thereof, wherein the formulation is formulated for oral administration and is suitable for treating asthma.

2. The formulation of claim 1 , wherein the bitter agent for an asthma formulation is DA.

3. A dose of the formulation of claim 2 , comprising a dosage of DA of from about 10 mg to about 400 mg.

4. The dose of claim 3 , wherein the dosage is from about 10 mg to about 200 mg.

5. The dose of claim 4 , wherein the dosage of DA is from about 10 mg to about 100 mg.

6. A method for treating asthma, comprising orally administering a synergistic formulation comprising a bitter agent and formoterol to a subject having asthma, wherein the bitter agent is chosen from denatonium acetate (DA), denatonium citrate (DC), denatonium maleate (DM).

7. The method of claim 6 , wherein the bitter agent is DA.

8. The method of claim 7 , wherein the subject is an adult and the daily dosage of DA is from about 10 mg to about 400 mg.

9. The method of claim 8 , wherein the subject is an adult and the daily dosage of DA is from about 10 mg to about 200 mg.

10. The method of claim 9 , wherein the subject is an adult and the daily dosage of DA is from about 10 mg to about 100 mg.

11. The method of claim 6 , wherein the subject is a human.

12. The method of claim 6 , wherein the subject is an adult human.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 27, 2020
From: LEE, TIEN-LI; ZHENG, ZHENHUAN
To: AARDVARK THERAPEUTICS INC
Reel/Frame 054750/0302 →
Continuity (2)
Provisional Application 62693255 · Jul 2, 2018
Related Publication 20210161838A1 · Jun 3, 2021
References Cited (40)
US 6068833A · Aberg · 2000 [cited by examiner]
US 7939671B2 · Li · 2011 [cited by applicant]
US 8062627B2 · Aberg · 2011 [cited by examiner]
US 8445692B2 · Karanewsky · 2013 [cited by applicant]
US 8796233B2 · Goddard · 2014 [cited by applicant]
US 9272051B2 · Goddard · 2016 [cited by applicant]
US 9579315B2 · Liggett · 2017 [cited by examiner]
US 10330678B2 · Goddard · 2019 [cited by applicant]
US 10610500B2 · Pharma · 2020 [cited by applicant]
US 10835505B2 · Lee · 2020 [cited by applicant]
US 20130131108A1 · Ligget et al. · 2013 [cited by applicant]
US 20140030332A1 · Baron · 2014 [cited by applicant]
US 20140302528A1 · Li · 2014 [cited by applicant]
US 20170227548A1 · Henkin · 2017 [cited by applicant]
US 20180161298A1 · Deretic · 2018 [cited by applicant]
WO WO2008024490 · 2008 [cited by applicant]
WO WO2012021291A2 · 2012 [cited by examiner]
WO WO2016172479 · 2016 [cited by applicant]
Berge et al. J Pharm Sci. Jan. 1977;66(1):1-19, published Jan. 1, 1977 (Year: 1977). [cited by examiner]
Souter et al., United States Patent Application Publication US 2015/0252304 A1, Pub. Date: Sep. 10, 2015, pp. 1-13 (Year: 2015). [cited by examiner]
Kumar et al. (Pharmaceutical Technology, Mar. 2008, 32, 3). (Year: 2008). [cited by examiner]
Zhai et al. “Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms” Oncotarget :21156-21167, 2016. [cited by applicant]
Deckmann et al., “Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes ” Proc. Natl. Acad. Sci. 111:8287-8292, 2014. [cited by applicant]
Upadhyaya et al., PLOS One 9:e110373, Dextromethorphan Mediated Bitter Taste Receptor Activation in the Pulmonary Circuit Causes Vasoconstriction. [cited by applicant]
Manson et al., “Bitter taste receptor agonists mediate relaxation of human and rodent vascular smooth muscle ” Eur. J. Pharmacology 740:302-311, 2014. [cited by applicant]
Pulkkinen et al., “The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea” Am. J. Physiol. Lung Cell Mol. Physiol. 303:956-966, 2012. [cited by applicant]
Sai et al. “Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K+” Clin. Exper. Pharmacology and Phys. 41:301-301, 2014. [cited by applicant]
Gassin-Delyle et al., “The expression and relaxant effect of bitter taste receptors on human bronchi” Respiratory Research 14:134, 2013. [cited by applicant]
Deloose et al. “Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers1” Am. J. Clin. Nutr. 105:583-588, 2017. [cited by applicant]
Avau et al. “Targeting extra-oral bitter taste receptors modulates gastrointestinal motility with effects on satiation” Scientific Reports 5:15985 2015. [cited by applicant]
Avau et al.2 “The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolismi n Mice” PLOS One 10.1371 2015. [cited by applicant]
Glendinning et al., “Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents” Physiol. Behav. 93:757-765, 2008. [cited by applicant]
Hao et al., “Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands” Am. J. Physiol. Regul. Integr. Comp. Physiol. 294:R33-R38, 2008. [cited by applicant]
Janssen et al., “Bitter taste receptors and a-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying ” PNAS 108:2094-2099, 2011. [cited by applicant]
Kim et al., “Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways” Diabetologia 57:2117-2125, 2014. [cited by applicant]
Miyata et al. “Effect of five taste ligands on the release of CCK from an enteroendocrine cell line, STC-1” Biomedical Research 35:171-176, 2014. [cited by applicant]
Schier et al. “Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal “bitter taste” cue” Am. J. Physiol. Regul. Integr. Comp. Physiol. 301:R1557-R1568, 2011. [cited by applicant]
Straub et al., “Stimulation of Insulin Secretion by Denatonium, One of the Most Bitter-Tasting Substances Known ” Diabetes 52:356-364, 2003. [cited by applicant]
Meyerhof et al., “The Molecular Receptive Ranges of Human TAS2R Bitter Taste Receptors” Chem. Senses 35:157-170. 2010. [cited by applicant]
PCT/US2019/040432 written opinion. [cited by applicant]